This is a competitive renewal of the Western New England Pediatric AIDS Clinical Trials Unit (WNEPACTU) and is submitted in conjunction with the Pediatric AIDS Clinical Trials Unit Group (PACTG) Coordinating and Operations Center (CORC) application. The WNEPACTU was established in 1992 and consists of a main unit at the University of Massachusetts Medical School, Worcester, MA and two subunits located at Baystate Medical Center in Springfield, MA and the University of CT Health Science Center in Farmington, CT. The WNEPACTU has been a national and international leader in the study of the pathogenesis of vertical HIV-1 infection. Investigators from WNEPACTU have held PACTG leadership positions and have played a major role in the development and accomplishment of the scientific agenda. The primary objectives of the WNEPACTU are: 1. To improve our understanding of the pathogenesis of HIV-1 infection in infants, children, and adolescents and to improve treatment strategies for all stages of pediatric HIV-1 infection (Primary Therapy RAC). 2. To improve our understanding of the pathogenesis of vertical HIV-1 transmission and to improve strategies to prevent vertical HIV-1 globally (Perinatal RAC). 3. To improve our understanding of the immunopathogenesis of pediatric HIV -1 infection, to evaluate the capacity for and potential role of immunomodulatory agents in immune reconstitution following antiretroviral therapy, and to evaluate vaccine approaches to prevent vertical and pediatric HIV-1 infection (Immunology/IBT/RAC). 4. To define potential adverse outcomes of antiretroviral therapy, to improve strategies to prevent or treat complications of HIV-1 infection or antiretroviral therapy, to better understand determinants of medication adherence in pediatric populations, and to improve the overall quality of life for HIV-1 infected children and their families (Complications of HIV RAC). 5. To improve our understanding of the viral and immunopathogenesis of adolescent HIV-1 infection and, in turn, improve strategies to prevent or treat adolescent HIV-1 infection (Adolescent Committee). Our history of scientific contributions, performance, and leadership coupled with our unique expertise to help answer the scientific agenda makes the WNEPACTU an ideal site for continued membership in the Pediatric AIDS Clinical Trials Group.